T- and B-cell functions and epitope expression in nonhuman primates immunized with simian immunodeficiency virus antigen by the rectal route.
T- and B-cell functions and epitope expression in nonhuman primates immunized with simian immunodeficiency virus antigen by the rectal route.
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通过直肠途径用猿猴免疫缺陷病毒抗原免疫的非人灵长类动物中的 T 细胞和 B 细胞功能以及表位表达。
DOI：
10.1073/pnas.90.18.8638
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发表时间：
1993
影响因子：
11.1
通讯作者：
J. Gearing
中科院分区：
文献类型：
--
作者：
T. Lehner;R. Brookes;C. Panagiotidi;L. Tao;L. Klavinskis;J. Walker;P. Walker;R. Ward;L. Hussain;J. Gearing
在北美和欧洲，人类免疫缺陷病毒（HIV）的传播最常见的是通过同性性交时的直肠粘膜。猴免疫缺陷病毒（SIV）猕猴模型已被用于研究直肠免疫。使用的疫苗是表达为杂合Ty病毒样颗粒（Ty-VLP）的重组SIV gag p27。将顺序口直肠（OR）粘膜免疫与i.m.次免疫而这两种途径的免疫诱导血清伊加和IgG p27抗体，只有OR免疫诱导直肠分泌伊加抗体。在i.m.免疫后，除血液和脾脏外，髂内淋巴结和肠系膜下淋巴结中也发现了它们。从外周血或淋巴样细胞生长的短期细胞系（STCL）的增殖反应的T细胞表位作图揭示了在任一免疫途径后多肽121-150内的主要表位。在脾细胞和循环细胞的STCL中，在肽41-80内发现了两个次要的T细胞表位。血清或胆汁伊加和IgG抗体的B细胞表位作图揭示了多肽121-170和51-90内的T细胞表位的两个重叠或相邻的免疫显性表位。结果表明，直肠增强口服免疫与重组颗粒抗原在非人灵长类动物eliminants分泌伊加和IgG反应在引流淋巴结和直肠粘膜在较小程度上，而系统免疫主要针对脾脏和循环T-和B-细胞反应。这些发现可能对预防艾滋病病毒感染同性性传播的疫苗设计策略具有重要意义。
Transmission of human immunodeficiency virus (HIV) in North America and Europe occurs most commonly through the rectal mucosa during homosexual intercourse. The simian immunodeficiency virus (SIV) macaque model has been used to investigate rectal immunization. The vaccine used was a recombinant SIV gag p27 expressed as hybrid Ty virus-like particles (Ty-VLP). Sequential ororectal (OR) mucosal immunization was compared with i.m. immunization. Whereas both routes of immunization induced serum IgA and IgG p27 antibodies, only OR immunization induced rectal secretory IgA antibodies. Specific CD4+ T-cell proliferative responses to stimulation with p27 were found after i.m. immunization only in the blood and spleen, but after OR immunization they were found in the internal iliac and inferior mesenteric lymph nodes in addition to the blood and spleen. T-cell epitope mapping of the proliferative responses of short-term cell lines (STCLs) grown from peripheral blood or lymphoid cells revealed a major epitope within the polypeptide 121-150 after either route of immunization. Two minor T-cell epitopes were found within peptide 41-80 in STCLs from splenic and circulating cells. B-cell epitope mapping of serum or biliary IgA and IgG antibodies revealed two overlapping or adjacent immunodominant epitopes to the T-cell epitopes within the polypeptides 121-170 and 51-90. The results suggest that rectal augmented by oral immunization with a recombinant particulate antigen in nonhuman primates elicits secretory IgA and to a lesser extent IgG responses in the draining lymph nodes and the rectal mucosa, whereas systemic immunization targets predominantly splenic and circulating T- and B-cell responses. These findings may have important implications in the strategy of designing vaccines in prevention of homosexual transmission of HIV infection.